Biomedical subjects

H Kainulainen

Publications and source records attributed to H Kainulainen.

At least 37 records · Page 2Linked to original sources

PubMed1994

Cloning of two novel ADP-ribosylation factor-like proteins and characterization of their differential expression in 3T3-L1 cells.

A polymerase chain reaction-based cloning approach was employed in order to identify ADP-ribosylation factors (ARF) in murine 3T3-L1 cells and to study their expression before and after differentiation of cells to the adipocyte-like phenotype. Partial sequences comprising the effector domains of ARF were amplified with degenerate primers and cloned. Five of these sequences were identified as murine homologues of known human ADP-ribosylation factors (ARF 1, 2, 4, 5, and 6). In addition, partial sequences of two previously unknown isoforms were found, and complete cDNA clones were isolated from a rat fat cell library and were sequenced. Both sequences harbor a putative myristoylation site in position 2, the known consensus sequences presumably involved in GTP binding and hydrolysis, and lack cysteine residues in the C terminus. Their amino acid sequences share a 56 and 41% identity, respectively, with human ARF 1. Based on a comparison with the known ARF isoforms, the first clone appears to represent the mammalian homologue of a known sequence from Drosophila (dARL 1, 79% identity) and was therefore designated rARL 1. The second clone resembled none of the known ARF-like proteins and was designated rARL 4. mRNA of ARL 4 was undetectable in the fibroblasts but abundant in the adipocyte-like phenotype, its expression starting on day 6 of the differentiation. In contrast, ARF 1, 2, and 5 were unaltered by differentiation of the 3T3-L1 cells; mRNA levels of ARF 6, and also of ARL 1 and ARF 4, were reduced after differentiation. It is suggested that the function of ARL 4 is related to the adipocyte-like phenotype of 3T3-L1 cells.

3T3 Cells↗

PubMed1994

In vivo glucose uptake and glucose transporter proteins GLUT1 and GLUT4 in heart and various types of skeletal muscle from streptozotocin-diabetic rats.

The in vivo glucose uptake and the levels of two glucose transporter proteins (GLUT1 and GLUT4) were measured in heart and in various types of skeletal muscle from streptozotocin-diabetic rats. Diabetes (12-16 weeks) reduced the in vivo glucose uptake (glucose metabolic index, GMI), and the levels of GLUT1 and GLUT4 in heart by 75%, 60% and 70%, respectively. In diaphragm consisting of approximately equal amounts of type I (slow-contracting oxidative), IIa (fast-contracting oxidative) and IIb (fast-contracting glycolytic) fibers, GMI and GLUT4 levels were reduced by 60% and 40%, respectively, with no change in GLUT1 levels. In muscle consisting mainly of type I fibers (e.g., m. soleus), GMI and GLUT4 levels were reduced by 60% and 30%, respectively, whereas GLUT1 levels were unaltered. In mixed-type muscle consisting of type IIa and IIb fibers (e.g., m. plantaris and red part of m. gastrocnemius), GMI and GLUT1 levels were unchanged, whereas GLUT4 levels were decreased by 45%. In contrast, GMI was increased by 100% in type IIb fibers (e.g., the white part of m. gastrocnemius), probably reflecting the 4-fold increase in blood glucose levels, whereas GLUT4 levels were lowered by 55% with no change in GLUT1 levels. These data demonstrate a marked difference in the response of in vivo glucose uptake to long-term hypoinsulinemia between oxidative (type I) and glycolytic (type IIb) fibers. Furthermore, in contrast to the GLUT4, GLUT1 levels are regulated differentially in heart and skeletal muscle in response to streptozotocin-induced diabetes.

Animals↗

PubMed1994

Dissociation of the effects of training on oxidative metabolism, glucose utilisation and GLUT4 levels in skeletal muscle of streptozotocin-diabetic rats.

The effects of long-term, moderate physical exercise on in vivo glucose uptake, levels of two glucose transporter proteins (GLUT1 and GLUT4) and activities of various key enzymes of energy metabolism were measured in skeletal muscle from streptozotocin-diabetic rats. Diabetes (12-16 weeks) reduced the in vivo glucose uptake (glucose metabolic index, GMI) in muscle containing mainly type I fibres by 55% but had no effect in muscles containing mainly type IIa and IIb fibres. GMI was increased in the diabetic white skeletal muscle (mainly type IIb fibres) by more than 120%. In contrast to the complex changes in GMI, GLUT4 levels were reduced in all types of skeletal muscle from diabetic rats with no change in GLUT1 levels. Exercise training had no effects on GMI or the glucose transporter levels. Streptozotocin induced diabetes significantly reduced the oxidative capacity of skeletal muscle assayed as the activities of citrate synthase, succinate dehydrogenase and cytochrome c oxidase. Training increased the activities of oxidative enzymes, with this increase being more prominent in the diabetic animals. The present data indicate that long-term streptozotocin-induced diabetes decreases oxidative metabolic capacity and GLUT4 protein levels in skeletal muscle, but that the changes of glucose transport largely depend on the fibre type composition. Moderate training fully reverses the effect of insulinopenia and hyperglycaemia on muscle oxidative metabolism. In contrast to the previous suggestions, the expression of GLUT4 is not correlated with the capacity of oxidative metabolism in skeletal muscle of streptozotocin-diabetic rats.

Animals↗

PubMed1993

Activities of antioxidant enzymes and lipid peroxidation in endometrial cancer.

Antioxidant enzyme activities and lipid peroxidation were analysed in normal endometrium and endometrial cancer tissues from Finnish and Japanese patients. The catalase and glutathione peroxidase activities of normal endometrium were significantly lower in Finns than in Japanese. Lipid peroxidation was slightly higher in endometrial cancer as compared with normal endometrium both in the Finns and in the Japanese. When cancer tissues were compared with normal endometrium both in Finns and Japanese the activity of superoxide dismutase was significantly lower in cancer tissue than in normal endometrium. In Finns glutathione S-transferase activity was also lower in endometrial cancer tissue than in normal endometrium, and a similar tendency was also found in Japanese. This study suggests that endometrial cancer tissue is associated with an impaired enzymic antioxidant defence system.

Catalase↗

PubMed1993

In-vivo glucose uptake and glucose transporter proteins GLUT1 and GLUT3 in brain tissue from streptozotocin-diabetic rats.

The effects of streptozotocin-induced diabetes (13 weeks) on the in-vivo glucose uptake and on the protein levels of glucose transporters in rat brain were studied and compared with those in cardiac muscle. Diabetes reduced the uptake of 2-[3H]deoxyglucose into lobus frontalis by 70%. However, uptake rates corrected for the 4-fold increase in serum glucose (glucose metabolic index, GMI) were essentially unaltered. The levels of glucose transporter proteins GLUT1 and GLUT3 in crude membranes from brain as assessed by immunoblotting were unaffected by diabetes, whereas GMI and levels of glucose transporters GLUT1 and GLUT4 in heart were reduced by 80 and 65%, respectively. Thus, glucose uptake and levels of glucose transporters in brain, unlike that in insulin sensitive tissues, are normal in long-term hypo-insulinaemia.

Animals↗

PubMed1992

Phenotypes of conjunctival inflammatory cells in sarcoidosis.

Phenotypes of the infiltrating mononuclear cells of the lower fornix conjunctiva of nine patients with sarcoidosis and six controls were studied using monoclonal antibodies and a modified immunoperoxidase method. Four patients had sarcoidosis of recent onset (duration of 2 years or less) and five patients had a chronic disease (duration of 3 or more years). The inflammatory cells in the sarcoid conjunctival specimens were predominantly T lymphocytes, the vast majority of which were of T helper/inducer subtype expressing Leu-3a + 3b positivity. The ratio of T helper/inducer cells to T suppressor/cytotoxic cells was 3.9 on average but only 0.9 in controls. Epithelioid cell granulomas were seen in three specimens in one case of recent onset and in two chronic cases comprising a marked amount (more than 15 cells/visual field) of cells bearing phenotypes of macrophages, T cells, T helper/inducer cells and HLA-DR antigen, and in smaller quantities of T suppressor/cytotoxic cells. The mean number of all immunocompetent cell subtypes of specimens from newly diagnosed patients exceeded that of specimens from chronic patients. We believe that the sarcoid immune reaction in the conjunctiva is a dynamic process in which proliferation of immunocompetent mononuclear cells precedes the stage of granuloma formation.

Adult↗

PubMed1991

Effects of training and anabolic steroids on collagen synthesis in dog heart.

The effects of endurance training and anabolic steroid (Methandienone 1.5 mg.kg-1 p. o. daily) and their combination on regional collagen biosynthesis and concentration in the hearts of male beagle dogs were studied by measuring prolyl 4-hydroxylase (PH) activity and hydroxyproline (HYP) concentration. The PH (P less than 0.05) and HYP (P less than 0.05) were both greater in the subendocardinal layer than in the subepicardium (EPI) of the left ventricular wall in controls, whereas opposite gradients (P less than 0.05) were observed in the right ventricle. Endurance exercise caused an increase of PH activity in EPI of the left ventricular wall (P less than 0.01). The HYP concentration increased in both layers of the right ventricle in the exercise plus steroid group (P less than 0.05). The results suggest that transmural differences exist in the rate of collagen synthesis and concentration in canine cardiac ventricles and that endurance exercise may accelerate collagen synthesis in EPI of the left ventricle and the combination of exercise and anabolic steroid causes an increase in collagen concentration in the right ventricular wall.

Alkaline Phosphatase↗

PubMed1991

Coronary pressure determines regional glucose uptake in the left ventricular wall of the heart.

The effect of coronary and intraventricular pressures on the glucose uptake and its transmural distribution was studied in isolated, beating rat heart perfused using the Langendorff procedure. Left ventricular glucose uptake measured by the deoxyglucose method, and the effect of coronary (aortic) pressure was dissociated from intraventricular pressure development by draining the left ventricle. Left ventricular glucose uptake was 2.6 +/- 0.1 mumols/min per g protein (mean +/- S.E.M.) and 35 +/- 6% higher (P less than 0.001) in the subendocardium than in the subepicardium under control conditions (aortic pressure 80 cm H2O, non-drained). Elimination of the intraventricular pressure development caused no significant change in the total left ventricular glucose uptake or its transmural distribution. Increase in the aortic pressure to 150 cmH2O accelerated glucose uptake in non-drained and drained hearts by 57-75%. The increase in the glucose uptake was more pronounced in the subepicardial layer than in the subendocardial layer, so that the transmural gradient decreased by 27-32% (P less than 0.001) in non-drained and drained hearts. The results indicate that in Langendorff-perfused heart the effect of aortic pressure on the total glucose uptake and its transmural distribution across the left ventricular wall is not mediated through intraventricular pressure development, but through the coronary pressure.

Animals↗

PubMed1991

Gastric parietal, chief, and G-cell densities in chronic renal failure.

We calculated morphometrically the amount of antral gastrin-producing (G) cells and body parietal and chief cells in gastric biopsy specimens from 30 undialysed patients with chronic renal failure (CRF) and from sex- and age-matched controls. The CRF patients had raised fasting serum gastrin levels, whereas these were normal in the controls (mean, 290 +/- 283 (+/- SD) ng/l (n = 27) versus 33 +/- 36 (n = 30)). Serum gastrin values of the patients and controls correlated positively with G-cell density (r = 0.501, n = 36, p = 0.002), as did the maximal acid output of the CRF patients with parietal cell density (r = 0.617, n = 14, p = 0.019). In CRF patients the densities of G, parietal, and chief cells were higher than those in the controls (G cells, 351 +/- 151 (+/- SD) cells/mm2, n = 21 versus 211 +/- 90, n = 16, p = 0.002; parietal cells, 299 +/- 94, n = 15 versus 224 +/- 72, n = 14, p = 0.025; chief cells, 886 +/- 346, n = 15 versus 743 +/- 182, n = 14, p = 0.181). The results agree with previous findings indicating that hyposecretion of gastric acid in CRF does not derive from decreased capacity for acid secretion but rather from the inhibition of acid output. Increased parietal cell density in CRF patients gives cause to suspect that the maximum acid output might even in raised, possibly depending on the permanent hypergastrinaemic state with its trophic influence on the gastric body mucosa.

Adult↗

PubMed1989

Enzymatic and nonenzymatic lipid peroxidation capacities and antioxidants in hypoxic and reoxygenated rat myocardium.

The effects of 60 min hypoxia and subsequent reoxygenation for 30 min on enzymatic (NADPH-dependent) and nonenzymatic (Fe2+/ascorbate-induced) lipid peroxidation capacities and on antioxidant levels were studied using Langendorff-perfused rat hearts. The assays were done on the myolayer of the right ventricle (RV) and on the subepi- and subendomyolayers of the left ventricle (epi/endo LV) after normoxic, hypoxic, and reoxygenation phases. The region injured by hypoxia/reoxygenation was located mainly in endo LV, seen as a lesser penetration of the fluorescent dye fluorescein in the myocardium. The electron microscopic findings after reoxygenation revealed swelling of the mitochondria, amorphous mitochondrial structures, and formation of paracrystallines. The myofibrillar structure of the cells was disrupted and the cells showed marked fluid accumulation. Membrane structures were marginated and formed blebs and multilamellar bodies. Ultrastructural changes were most prominent in endo LV, especially after reoxygenation. The increase in leakage of lactate in the perfusate revealed the onset of anaerobic metabolism. Abrupt release of the cytoplasmic enzymes lactate dehydrogenase and creatine kinase at the beginning of the reoxygenation phase suggested cell membrane injury. The capacity for Fe2+/ascorbate-induced lipid peroxidation slightly increased in RV and that for NADPH-dependent, enzymatic lipid peroxidation in endo LV after reoxygenation. Catalase, glutathione peroxidase, and superoxide dismutase activities remained unchanged, whereas glucose-6-phosphate dehydrogenase activity decreased after reoxygenation in RV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Training increases cardiac glucose uptake during rest and exercise in rats.

The effect of chronic exercise on the regional glucose uptake in the left ventricle of the heart was studied in resting and swimming rats using the 2-deoxyglucose method. The left ventricular glucose uptake of untrained resting controls averaged 1.7 +/- 0.1 mumol.min-1.g protein-1 and that of chronically trained resting rats 3.5 +/- 0.3 mumol.min-1.g protein-1 (P less than 0.001). During a 20-min swimming period the glucose uptake rate of untrained rats was 2.3 +/- 0.1 mumol.min-1.g protein-1 and that of trained rats 3.4 +/- 0.3 mumol.min-1.g protein-1 (P less than 0.01). The subendocardial glucose uptake was 25% higher than the subepicardial uptake in the resting control group, whereas no gradient was observed in the other groups. The product of heart rate and blood pressure during swimming increased by 60-70% in the untrained and trained groups. The increase in total left ventricular glucose uptake and its transmural distribution by training seemed to be independent of the actual oxygen consumption or supply of major alternative myocardial substrates.

Animals↗

PubMed1989

Effects of training on regional substrate oxidation in the hearts of ageing rats.

23-month-old male rats were trained by running for 20 weeks. The oxidation rates of succinate, glutamate+malate, palmitoylcarnitine, and pyruvate and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in the subendocardium and subepicardium and in the right ventricle. Regional differences of substrate oxidation rates in the myocardium of old sedentary or trained rats were less than in young rats, suggesting that regional differences in the cardiac work load disappear during ageing. Training did not improve oxidation rates, in contradiction to some previous results.

Aging↗

PubMed1988

Protein synthesis and cyclic GMP content in rat cardiac muscle after swimming exercise.

Rats were exercised for 6 h by swimming. Phenylalanine incorporation into myocardial proteins was increased when 2 h had elapsed after the termination of exercise. Cyclic GMP concentration did not change during the experiment, which indicates that cyclic GMP does not act directly as a trigger of myocardial protein synthesis in volume overload.

Animals↗

PubMed1988

Transmural distribution of biochemical markers of total protein and collagen synthesis, myocardial contraction speed and capillary density in the rat left ventricle in angiotensin II-induced hypertension.

The effect of angiotensin II-induced hypertension on selected biochemical parameters was studied in Sprague-Dawley rats. Angiotensin II infusion at rates of 41.7 micrograms h-1 kg-1 and 12.5 micrograms h-1 kg-1 for 2, 5, 10 and 15 days elevated the systolic blood pressure from 143 +/- 7 mmHg to 215-230 mmHg (P less than 0.001) and 185-195 mmHg (P less than 0.001), respectively. The left ventricular weight/body weight ratio increased 10-14% (P less than 0.05) and 23-32% (P less than 0.001) after 2-15 days in rats treated at the lower and higher infusion rates, respectively. Prolyl 4-hydroxylase (PH) activity, a marker of collagen synthesis, was evenly distributed in the left ventricle. PH activity increased by about 100% in both subendocardial and subepicardial layers of the left ventricular wall after angiotensin II infusion for 10 days at 41.7 micrograms h-1 kg-1, but remained unaltered at 12.5 micrograms h-1 kg-1. No change was observed in hydroxyproline concentration. Myosin isoenzymes (V1-V3), which reflect myocardial contractility, were unevenly distributed in the left ventricular wall: the proportion of the fast-turnover isoenzyme (V1) was smaller in the subendocardial layer than in the subepicardial layer. The proportion of V1 decreased after treatment in both layers. Alkaline phosphatase activity, a marker of capillary density, was evenly distributed transmurally in the left ventricular wall. Angiotensin II caused a slight decrease in this activity in both myocardial layers. The results suggest that the elevation of blood pressure leads to transmurally evenly distributed changes in biochemical parameters reflecting collagen synthesis, capillary density and contractile properties of the myocardium.

Alkaline Phosphatase↗

PubMed1985

Redistribution of glucose uptake by chronic exercise, measured in isolated perfused rat hearts.

The effects of 8-9 weeks of running and swimming training on the transmural distribution of cardiac glucose uptake and protein synthesis in isolated perfused heart were studied in male rats. The left ventricular glucose uptake in hearts from sedentary rats was 2.5 +/- 0.3 mumoles/min per g protein (mean +/- S.D.), and about 30% higher in the subendocardial layer than in the subepicardial layer (P less than 0.01). After the running and swimming programs the total left ventricular glucose uptake was at the level of sedentary rats, but the gradient was absent. The rate of protein synthesis was evenly distributed through the left ventricular wall and similar in all experimental groups. The altered transmural distribution of glucose uptake after exercise probably reflects differences in the adaptive response of various myocardial muscle layers to a long-term intermittent increase in the cardiac work load.

Animals↗

PubMed1984

Endurance training and antioxidants of lung.

Mice and rats were adjusted to daily treadmill training programs, which were heavy enough to increase the oxidative capacity of skeletal muscles. Endurance training did not affect the activities of catalase and glutathione peroxidase and the concentration of vitamin E in the lungs of mice and rats. Thus increased ventilation and oxygen utilization induced by exercise training do not modify lung antioxidants, in contrast to hyperoxia and hypoxia.

Animals↗

PubMed1984

Endurance training decreases the alkaline proteolytic activity in mouse skeletal muscles.

Alkaline and myofibrillar protease activities of rectus femoris, soleus, and tibialis anterior muscles and the pooled sample of gastrocnemius and plantaris muscles were analyzed in male NMRI-mice during a running-training program of 3, 10, or 20 daily 1-h sessions. The activity of citrate synthase increased during the endurance training, reflecting the increased oxidative capacity of skeletal muscles. The activities of alkaline and myofibrillar proteases continually decreased in the course of the training program in all muscles studied. Instead, the activity of beta-glucuronidase (a marker of lysosomal hydrolases) increased in all muscles. The highest activities were observed at the beginning of the training program. Present results, together with our earlier observations, show that the type of training, running as opposed to swimming, modulates the training responses in alkaline protease activities. Further, diverse adaptations in the activities of alkaline proteases and a lysosomal hydrolase suggest difference in the function of different proteolytic systems.

Animals↗

PubMed1984

Vitamin E deficiency and the susceptibility to lipid peroxidation of mouse cardiac and skeletal muscles.

Effects of a short-term vitamin E deficiency on some lipid peroxidative properties were investigated in mouse cardiac and skeletal muscles. The concentration of vitamin E decreased 35.8% in 5 weeks and 61.2% in 12 weeks in skeletal muscle. The corresponding decrease in cardiac muscle was 65.7% in 12 weeks. Simultaneously the susceptibility of muscle homogenates to in vitro lipid peroxidation increased with 48.6% (5 weeks) and 44.5% (12 weeks) in skeletal muscle and with 101.8% (12 weeks) in cardiac muscle. Highly significant negative correlations were observed between the concentration of vitamin E and in vitro lipid peroxidation in cardiac and skeletal muscles. Also the sensitivity to Fe2+-induced peroxidation was increased in skeletal muscle after the deficiency of 5 weeks. The total contents of peroxidizable lipids (Fe2+-induction) were significantly (approx. 20%) decreased after 12 weeks in cardiac and skeletal muscles. The concentration of lipofuscin was unaffected in both muscles of vitamin E-deficient mice. Vitamin E deficiency (5 weeks) decreased the activity of selenium-dependent glutathione peroxidase in skeletal muscle but did not affect the activities of catalase and beta-glucuronidase and the concentrations of protein, reduced glutathione and total sulfhydryl groups. These results show that a short-term vitamin E deficiency affects the peroxidative properties of cardiac and skeletal muscles and may thus expose the muscles to peroxidation injuries.

Animals↗